Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats

Abstract

Oxidative stress and suppressed H₂S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H₂S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n = 6) were treated for 4 weeks either as controls or received NaHS (SHR + NaHS), tempol (SHR + Tempol), or NaHS plus tempol (SHR + NaHS + Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0 ± 2 vs. 100.0 ± 3 mmHg), lower plasma and urinary H₂S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all p < 0.05). Treatment either with NaHS or with tempol alone decreased blood pressure and oxidative stress and improved renal hemodynamic and excretory function compared to untreated SHR. Combined NaHS and tempol therapy in SHRs caused larger decreases in blood pressure (∼20–22% vs. ∼11–15% and ∼10–14%), increases in creatinine clearance, urinary sodium excretion and fractional sodium excretion and up-regulated the antioxidant status compared to each agent alone (all p < 0.05). These findings demonstrated that H₂S and tempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.

• Creatinine clearance
• H₂S
• oxidative stress
• SHR
• tempol

Acknowledgements

The authors fully acknowledge the Fundamental Research Grant no. 203/PFARMASI/6711217 provided by the Ministry of Science Technology and Innovation (MOSTI), Government of Malaysia, for this work.